It is proposed to use phospholipid vesicles (liposomes) as "carriers" for introducing pharmacologically active compounds into cells both in vitro and in vivo. It is well established that lipid vesicles are taken up avidly by cultured cells in vitro. Furthermore, evidence from this and other laboratories indicates that an important route for cellular incorporation is fusion of the vesicles with the plasma membrane of the cell. The contents of the vesicle would thus be free to diffuse into the cytoplasm following such mechanism of incorporation. Recent evidence from our laboratory indicates that small unilamellar vesicles containing anti-tumor drugs produce a drastic increase of both the drug distribution to various tissues (including tumor cells) and its anti-tumor-activity, with normal and drug-resistant cells. We plan to use various drug-containing lipid vesicles to enhance the cellular incorporation of several chemotherapeutic agents that are not taken up normally by living cells or have very short plasma half-life in vivo. We will incorporate drugs into vesicles, characterize their uptake in vitro and assay their biological effects. We will study, in vivo, the rate of clearance of different vesicles from the blood, their distribution in different tissues and their anti-tumor effects. We will also study their uptake and cytotoxic effects against various drug-resistant tumor cells. The composition and size of the vesicles will be varied in order to obtain maximal drug sequestration and minimal leakage, and optimal plasma clearance rate, uptake by cells and tissue distribution. In addition we will investigate the possibility of making vesicles specifically targetted to specific cell types and tissues. Finally, we will further develop new procedures for the production of lipid vesicles with special properties such as total encapsulation of the available drug.